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The c-MYC allele that is translocated into the IgH locus undergoes constitutive hypermutation in a Burkitt's lymphoma line

Bemark, Mats LU orcid and Neuberger, Michael S. (2000) In Oncogene 19(30). p.3404-3410
Abstract

Burkitt's lymphomas harbour chromosomal translocations bringing c-MYC into the vicinity of one of the immunoglobulin gene loci. Point mutations have been described within c-MYC in several Burkitt's lymphomas and it has been proposed that translocation into the Ig loci might have transformed c-MYC into a substrate for the antibody hypermutation mechanism. Here we test this hypothesis by exploiting a Burkitt's lymphoma line (Ramos) that we have previously shown to hypermutate its immunoglobulin genes constitutively. We find that, during in vitro culture, Ramos mutates the c-MYC allele that is translocated into the IgH locus whilst leaving the untranslocated c-MYC and other control genes essentially unaffected. The mutations are introduced... (More)

Burkitt's lymphomas harbour chromosomal translocations bringing c-MYC into the vicinity of one of the immunoglobulin gene loci. Point mutations have been described within c-MYC in several Burkitt's lymphomas and it has been proposed that translocation into the Ig loci might have transformed c-MYC into a substrate for the antibody hypermutation mechanism. Here we test this hypothesis by exploiting a Burkitt's lymphoma line (Ramos) that we have previously shown to hypermutate its immunoglobulin genes constitutively. We find that, during in vitro culture, Ramos mutates the c-MYC allele that is translocated into the IgH locus whilst leaving the untranslocated c-MYC and other control genes essentially unaffected. The mutations are introduced downstream of the c-MYC transcription start with the pattern of substitutions being characteristic of the antibody hypermutation mechanism; the mutation frequency is 2-3-fold lower than for the endogenous functional IgH allele. Thus chromosomal translocations invoicing the Ig loci may not only contribute to transformation by deregulating oncogene expression but could also act by potentiating subsequent oncogene hypermutation.

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publishing date
type
Contribution to journal
publication status
published
keywords
c-MYC, Immunoglobulin genes, Somatic hypermutation
in
Oncogene
volume
19
issue
30
pages
3404 - 3410
publisher
Nature Publishing Group
external identifiers
  • pmid:10918597
  • scopus:0034644134
ISSN
0950-9232
DOI
10.1038/sj.onc.1203686
language
English
LU publication?
no
id
e1b632d9-5d72-4080-97a8-c7b05ef978fb
date added to LUP
2023-11-28 10:24:35
date last changed
2024-03-28 09:12:27
@article{e1b632d9-5d72-4080-97a8-c7b05ef978fb,
  abstract     = {{<p>Burkitt's lymphomas harbour chromosomal translocations bringing c-MYC into the vicinity of one of the immunoglobulin gene loci. Point mutations have been described within c-MYC in several Burkitt's lymphomas and it has been proposed that translocation into the Ig loci might have transformed c-MYC into a substrate for the antibody hypermutation mechanism. Here we test this hypothesis by exploiting a Burkitt's lymphoma line (Ramos) that we have previously shown to hypermutate its immunoglobulin genes constitutively. We find that, during in vitro culture, Ramos mutates the c-MYC allele that is translocated into the IgH locus whilst leaving the untranslocated c-MYC and other control genes essentially unaffected. The mutations are introduced downstream of the c-MYC transcription start with the pattern of substitutions being characteristic of the antibody hypermutation mechanism; the mutation frequency is 2-3-fold lower than for the endogenous functional IgH allele. Thus chromosomal translocations invoicing the Ig loci may not only contribute to transformation by deregulating oncogene expression but could also act by potentiating subsequent oncogene hypermutation.</p>}},
  author       = {{Bemark, Mats and Neuberger, Michael S.}},
  issn         = {{0950-9232}},
  keywords     = {{c-MYC; Immunoglobulin genes; Somatic hypermutation}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{30}},
  pages        = {{3404--3410}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Oncogene}},
  title        = {{The c-MYC allele that is translocated into the IgH locus undergoes constitutive hypermutation in a Burkitt's lymphoma line}},
  url          = {{http://dx.doi.org/10.1038/sj.onc.1203686}},
  doi          = {{10.1038/sj.onc.1203686}},
  volume       = {{19}},
  year         = {{2000}},
}